Multicentre, England-wide randomised controlled trial of the 'Foundations' smartphone application in improving mental health and well-being in a healthcare worker population.

BACKGROUND: Healthcare workers (HCWs) have faced considerable pressures during the COVID-19 pandemic. For some, this has resulted in mental health distress and disorder. Although interventions have sought to support HCWs, few have been evaluated. AIMS: We aimed to determine the effectiveness of the 'Foundations' application (app) on general (non-psychotic) psychiatric morbidity. METHOD: We conducted a multicentre randomised controlled trial of HCWs at 16 NHS trusts (trial registration number: EudraCT: 2021-001279-18). Participants were randomly assigned to the app or wait-list control group. Measures were assessed at baseline, after 4 and 8 weeks. The primary outcome was general psychiatric morbidity (using the General Health Questionnaire). Secondary outcomes included: well-being; presenteeism; anxiety; depression and insomnia. The primary analysis used mixed-effects multivariable regression, presented as adjusted mean differences (aMD). RESULTS: Between 22 March and 3 June 2021, 1002 participants were randomised (500:502), and 894 (89.2%) followed-up. The sample was predominately women (754/894, 84.3%), with a mean age of 44⋅3 years (interquartile range (IQR) 34-53). Participants randomised to the app had a reduction in psychiatric morbidity symptoms (aMD = -1.39, 95% CI -2.05 to -0.74), improvement in well-being (aMD = 0⋅54, 95% CI 0⋅20 to 0⋅89) and reduction in insomnia (adjusted odds ratio (aOR) = 0⋅36, 95% CI 0⋅21 to 0⋅60). No other significant findings were found, or adverse events reported. CONCLUSIONS: The app had an effect in reducing psychiatric morbidity symptoms in a sample of HCWs. Given it is scalable with no adverse effects, the app may be used as part of an organisation's tiered staff support package. Further evidence is needed on long-term effectiveness and cost-effectiveness.

Comparison between first and second wave of COVID-19 outbreak in older people: the COPE multicentre European observational cohort study.

BACKGROUND: Effective shielding measures and virus mutations have progressively modified the disease between the waves, likewise healthcare systems have adapted to the outbreak. Our aim was to compare clinical outcomes for older people with COVID-19 in Wave 1 (W1) and Wave 2 (W2). METHODS: All data, including the Clinical Frailty Scale (CFS), were collected for COVID-19 consecutive patients, aged ≥65, from 13 hospitals, in W1 (February-June 2020) and W2 (October 2020-March 2021). The primary outcome was mortality (time to mortality and 28-day mortality). Data were analysed with multilevel Cox proportional hazards, linear and logistic regression models, adjusted for wave baseline demographic and clinical characteristics. RESULTS: Data from 611 people admitted in W2 were added to and compared with data collected during W1 (N = 1340). Patients admitted in W2 were of similar age, median (interquartile range), W2 = 79 (73-84); W1 = 80 (74-86); had a greater proportion of men (59.4% vs. 53.0%); had lower 28-day mortality (29.1% vs. 40.0%), compared to W1. For combined W1-W2 sample, W2 was independently associated with improved survival: time-to-mortality adjusted hazard ratio (aHR) = 0.78 [95% confidence interval (CI) 0.65-0.93], 28-day mortality adjusted odds ratio = 0.80 (95% CI 0.62-1.03). W2 was associated with increased length of hospital stay aHR = 0.69 (95% CI 0.59-0.81). Patients in W2 were less frail, CFS [adjusted mean difference (aMD) = -0.50, 95% CI -0.81, -0.18], as well as presented with lower C-reactive protein (aMD = -22.52, 95% CI -32.00, -13.04). CONCLUSIONS: COVID-19 older adults in W2 were less likely to die than during W1. Patients presented to hospital during W2 were less frail and with lower disease severity and less likely to have renal decline.

The Prognostic and Discriminatory Utility of the Clinical Frailty Scale and Modified Frailty Index Compared to Age.

Background: There is no consensus on the optimal method for the assessment of frailty. We compared the prognostic utility of two approaches (modified Frailty Index [mFI], Clinical Frailty Scale [CFS]) in older adults (≥65 years) hospitalised with COVID-19 versus age. Methods: We used a test and validation cohort that enrolled participants hospitalised with COVID-19 between 27 February and 30 June 2020. Multivariable mixed-effects logistic modelling was undertaken, with 28-day mortality as the primary outcome. Nested models were compared between a base model, age and frailty assessments using likelihood ratio testing (LRT) and an area under the receiver operating curves (AUROC). Results: The primary cohort enrolled 998 participants from 13 centres. The median age was 80 (range:65-101), 453 (45%) were female, and 377 (37.8%) died within 28 days. The sample was replicated in a validation cohort of two additional centres (n = 672) with similar characteristics. In the primary cohort, both mFI and CFS were associated with mortality in the base models. There was improved precision when fitting CFS to the base model +mFI (LRT = 25.87, p < 0.001); however, there was no improvement when fitting mFI to the base model +CFS (LRT = 1.99, p = 0.16). AUROC suggested increased discrimination when fitting CFS compared to age (p = 0.02) and age +mFI (p = 0.03). In contrast, the mFI offered no improved discrimination in any comparison (p > 0.05). Similar findings were seen in the validation cohort. Conclusions: These observations suggest the CFS has superior prognostic value to mFI in predicting mortality following COVID-19. Our data do not support the use of the mFI as a tool to aid clinical decision-making and prognosis.

A rapid assessment of take-home naloxone provision during COVID-19 in Europe.

BACKGROUND: In March 2020, the World Health Organization declared COVID-19 a global pandemic. In the following weeks, most European countries implemented national lockdowns to mitigate viral spread. Services for people who use drugs had to quickly revise their operating procedures to rearrange service provision while adhering to lockdown requirements. Given the scarcity of literature published on overdose prevention during COVID-19 in Europe, we aimed to examine how these changes to service provision affected take-home naloxone (THN) programmes and naloxone availability across Europe. METHODS: Between November 2020 and January 2021, we conducted a rapid assessment with country experts from European countries that provide THN. We sent country experts a template to report monthly THN distribution data (January 1, 2019-October 31, 2020) and a structured 6-item survey for completion. RESULTS: Responses were received from 14 of the 15 European countries with THN provision of which 11 participated in the rapid assessment: Austria, Denmark, England, Estonia, Lithuania, Northern Ireland, Norway, Scotland, Spain (Catalonia only), Sweden, and Wales. All reported reduced organisational capacity during COVID-19, and some put into place a range of novel approaches to manage the restrictions on face-to-face service provision. In six countries, the introduction of programme innovation occurred alongside the publication of government guidelines recommending increased THN provision during COVID-19. Eight of the eleven participating countries managed to maintain 2019-level monthly THN distribution rates or even increase provision during the pandemic. CONCLUSION: Through programme innovation supported by public guidelines, many European THN programmes managed to ensure stable or even increased THN provision during the pandemic, despite social distancing and stay-at-home orders affecting client mobility.

Parental preferences for a mandatory vaccination scheme in England: A discrete choice experiment

Summary Background Mandatory vaccination has been mooted to combat falling childhood vaccine uptake rates in England. This study investigated parental preferences for a mandatory vaccination scheme. Methods Discrete choice experiment. Six attributes were investigated: vaccine, child age group, incentive, penalty, ability to opt out, and compensation scheme. Mixed effects conditional logit regression models were used to investigate parental preferences and relative importance of attributes. Findings Participants were 1,001 parents of children aged 5 years and under in England (53% female;mean age=33·6 years, SD=7·1;84% white). Parental preferences were mostly based on incentives (30·7% relative importance;80·9% [95% confidence interval 76·3–85·0%] preference for parent and 74·8% [71·0–78·3%] for child incentive;reference: no incentive) and penalties (25·4% relative importance;69·5% [65·7–73·1%] preference for schemes where unvaccinated children cannot attend school or day care and 67·6% [63·6–71·4%] for those withholding financial benefits for parents of unvaccinated children;reference: £450 fine). Parents also preferred schemes that: offered a compensation scheme (18·1% relative importance;66·4% [62·7–69·8%] preference;reference: not offered), mandated vaccination in children aged 2 years (versus 5 years;11·4% relative importance;42·6% [39·4–45·9%] preference;reference: 2 years), mandated the 6-in-1 vaccine (10·5% relative importance;58·2% [54·6–61·7%] preference;reference: MMR), and that offered only medical exemptions (versus medical and religious belief exemptions;4·0% relative importance;45·5% [41·1–50·0%] preference;reference: medical exemptions). Interpretation These findings can inform policymakers’ decisions about how best to implement a mandatory childhood vaccination scheme in England. Funding Data collection was funded by a British Academy/Leverhulme Small Research Grants (SRG1920\101118).

Frailty is associated with poor mental health 1 year after hospitalisation with COVID-19

Background Frailty is associated with long-term physical deterioration after COVID-19. Mental health recovery has been less well investigated. Early studies have shown minimal effect from the virus, although studies have not focused on whether people living with frailty may have different psychiatric outcomes. We aimed to examine the effect of living with frailty on mental health outcomes one year after hospital with COVID-19. Methods We undertook a multicentre cross-sectional study of people admitted with COVID-19. We assessed quality of life (ICECAP-O and MRC), psychiatric symptoms including: generalised anxiety (GAD-7), depression (Patient Health Questionnaire-9), and trauma (Trauma Screening Questionnaire). Frailty was measured using the Clinical Frailty Scale (CFS). We used a multivariable mixed-effects logistic and linear regression to examine the adjusted odds ratio (aOR) and adjusted mean difference (aMD). Results From eight hospitals 224 participants consented. Median follow-up time from admission 358 days (IQR 153–418), mean age 63.8 (SD = 13.7), 34.8% female (n = 78), and 43.7% living with frailty (n = 98 CFS 4–8). People living with frailty were significantly more likely to have symptoms of anxiety aOR = 5.72 (95% CI 1.71–19.13), depression aOR = 2.52 (95% CI 1.59–14.91), post-traumatic stress disorder aMD = 1.16 (95% CI 0.47, 1.85), and worse quality of life aMD = 1.06 (95% CI 0.76–1.36). Limitations Patient-rated symptoms were captured rather than formal mental health diagnoses. CFS has not been validated in under 65-year-olds. Conclusions Living with frailty is associated with significant psychiatric morbidity and reduced wellbeing one year after COVID-19 hospital admission. We recommend clinical follow-up after COVID-19 for people living with frailty should include a psychiatric assessment.

Impact of diabetes on COVID-19 mortality and hospital outcomes from a global perspective: An umbrella systematic review and meta-analysis.

INTRODUCTION: To date, COVID-19 has claimed 4.9 million lives. Diabetes has been identified as an independent risk factor of serious outcomes in people with COVID-19 infection. Whether that holds true across world regions uniformly has not been previously assessed. METHODS: This study offers the first umbrella systematic review and meta-analysis to analyse the collective and geographically stratified mortality, ICU admission, ventilation requirement, illness severity and discharge rate amongst patients with diabetes. Five databases (EMBASE, MEDLINE, CAB Abstracts, PsychInfo and Web of Science) and 3 additional sources (SSRN's eLibrary, Research Square and MedRxiv) were searched from inception to 30 August 2021. Prospective and retrospective cohort studies, reporting the association between diabetes and one or more COVID-19 hospitalization outcomes, were included. This meta-analysis was registered on PROSPERO, CRD42021278579. Abbreviated MeSH terms used for search were as follows: (Diabetes) AND (2019 Novel Coronavirus Disease), adapted per database requirements. Exclusion criteria exclusion criteria were as follows: (1) none of the primary or secondary outcomes of meta-analysis reported, (2) no confirmed COVID-19 infection (laboratory or clinical) and (3) no unexposed population (solely patients with diabetes included). Quality of the included studies were assessed using the Newcastle-Ottawa Scale (NOS) whilst quality of evidence by the GRADE framework. Studies that were clinically homogeneous were pooled. Summative data and heterogeneity were generated by the Cochrane platform RevMan (V. 5.4). RESULTS: Overall, 158 observational studies were included, with a total of 270,212 of participants, median age 59 [53-65 IQR] of who 56.5% were male. A total of 22 studies originated from EU, 90 from Far East, 16 from Middle East and 30 from America. Data were synthesized with mixed heterogeneity across outcomes. Pooled results highlighted those patients with diabetes were at a higher risk of COVID-19-related mortality, OR 1.87 [95%CI 1.61, 2.17]. ICU admissions increased across all studies for patients with diabetes, OR 1.59 [95%CI 1.15, 2.18], a result that was mainly skewed by Far East-originating studies, OR 1.94 [95%CI 1.51, 2.49]. Ventilation requirements were also increased amongst patients with diabetes worldwide, OR 1.44 [95%CI 1.20, 1.73] as well as their presentation with severe or critical condition, OR 2.88 [95%CI 2.29, 3.63]. HbA1C levels under <70 mmol and metformin use constituted protective factors in view of COVID-19 mortality, whilst the inverse was true for concurrent insulin use. CONCLUSIONS: Whilst diabetes constitutes a poor prognosticator for various COVID-19 infection outcomes, variability across world regions is significant and may skew overall trends.

Prognostic value of estimated glomerular filtration rate in hospitalised older patients (over 65) with COVID-19: a multicentre, European, observational cohort study.

BACKGROUND: The reduced renal function has prognostic significance in COVID-19 and it has been linked to mortality in the general population. Reduced renal function is prevalent in older age and thus we set out to better understand its effect on mortality. METHODS: Patient clinical and demographic data was taken from the COVID-19 in Older People (COPE) study during two periods (February-June 2020 and October 2020-March 2021, respectively). Kidney function on admission was measured using estimated glomerular filtration rate (eGFR). The primary outcomes were time to mortality and 28-day mortality. Secondary outcome was length of hospital stay. Data were analysed with multilevel Cox proportional hazards regression, and multilevel logistic regression and adjusted for individual patient clinical and demographic characteristics. RESULTS: One thousand eight hundred two patients (55.0% male; median [IQR] 80 [73-86] years) were included in the study. 28-day mortality was 42.3% (n = 742). 48% (n = 801) had evidence of renal impairment on admission. Using a time-to-event analysis, reduced renal function was associated with increased in-hospital mortality (compared to eGFR ≥ 60 [Stage 1&2]): eGFR 45-59 [Stage 3a] aHR = 1.26 (95%CI 1.02-1.55); eGFR 30-44 [Stage 3b] aHR = 1.41 (95%CI 1.14-1.73); eGFR 1-29 [Stage 4&5] aHR = 1.42 (95%CI 1.13-1.80). In the co-primary outcome of 28-day mortality, mortality was associated with: Stage 3a adjusted odds ratio (aOR) = 1.18 (95%CI 0.88-1.58), Stage 3b aOR = 1.40 (95%CI 1.03-1.89); and Stage 4&5 aOR = 1.65 (95%CI 1.16-2.35). CONCLUSION: eGFR on admission is a good independent predictor of mortality in hospitalised older patients with COVID-19 population. We found evidence of a dose-response between reduced renal function and increased mortality.

Multiple house occupancy is associated with mortality in hospitalized patients with COVID-19.

BACKGROUND: In response to the COVID-19 pandemic, many countries mandated staying at home to reduce transmission. This study examined the association between living arrangements (house occupancy numbers) and outcomes in COVID-19. METHODS: Study population was drawn from the COPE study, a multicentre cohort study. House occupancy was defined as: living alone; living with one other person; living with multiple other people; or living in a nursing/residential home. Outcomes were time from admission to mortality and discharge (Cox regression), and Day 28 mortality (logistic regression) analyses were adjusted for key comorbidities and covariates including admission: age, sex, smoking, heart failure, admission C-reactive protein (CRP), chronic obstructive pulmonary disease, estimated glomerular filtration rate, frailty and others. RESULTS: A total of 1584 patients were included from 13 hospitals across UK and Italy: 676 (42.7%) were female, 907 (57.3%) were male, median age was 74 years (range: 19-101). At 28 days, 502 (31.7%) had died. Median admission CRP was 67, 82, 79.5 and 83 mg/l for those living alone, with someone else, in a house of multiple occupancy and in a nursing/residential home, respectively. Compared to living alone, living with anyone was associated with increased mortality: within a couple [adjusted hazard ratios (aHR) = 1.39, 95% confidence intervals (CI) 1.09-1.77, P = 0.007]; living in a house of multiple occupancy (aHR = 1.67, 95% CI 1.17-2.38, P = 0.005); and living in a residential home (aHR = 1.36, 95% CI 1.03-1.80, P = 0.031). CONCLUSION: For patients hospitalized with COVID-19, those living with one or more people had an increased association with mortality, they also exhibited higher CRP indicating increased disease severity suggesting they delayed seeking care.

Psilocybin-assisted therapy for the treatment of resistant major depressive disorder (PsiDeR): protocol for a randomised, placebo-controlled feasibility trial.

INTRODUCTION: Psilocybin-assisted therapy may be a new treatment for major depressive disorder (MDD), with encouraging data from pilot trials. In this trial (short name: PsiDeR) we aimed to test the feasibility of a parallel-group, randomised, placebo-controlled design. The primary outcomes in this trial are measures of feasibility: recruitment rates, dropout rates and the variance of the primary outcome measure of depression. METHODS AND ANALYSIS: We are recruiting up to 60 participants at a single centre in London, UK who are unresponsive to, or intolerant of, at least two evidence-based treatments for MDD. Participants are randomised to receive a single dosing session of 25 mg psilocybin or a placebo. All participants receive a package of psychological therapy. The primary outcome measure for depression is the Montgomery Asberg Depression Rating Scale collected by blinded, independent raters. The primary endpoint is at 3 weeks, and the total follow-up is 6 weeks. With further informed consent, this study collects neuroimaging and omics data for mechanism and biomarker analyses and offers participants an open label extension consisting of a further, open label dose of 25 mg of psilocybin. ETHICS AND DISSEMINATION: All participants will be required to provide written informed consent. The trial has been authorised by the National Research Ethics Committee (20-LO/0206), Health Research Authority (252750) and Medicine's and Healthcare Products Regulatory Agency (CTA 14523/0284/001-0001) in the UK. Dissemination of results will occur via a peer-reviewed publication and other relevant media. TRIAL REGISTRATION NUMBERS: EUDRACT2018-003573-97; NCT04959253.

Long-term effects of COVID-19 on mental health: A systematic review.

BACKGROUND: Acute effects of COVID-19 can be life-threatening. Alterations in mental health during the active infection have been documented, but the long-term consequences are less clear. METHOD: A systematic review was undertaken to investigate the effect of COVID-19 infection on long-term mental health outcomes. Three databases [PubMed, Medline (Ovid) and Cochrane library] were searched between 1st October 2019 and 29th August 2021 with additional hand searching to identify all published studies reporting symptoms of generalised anxiety, depression, post-traumatic stress disorder (PTSD), or sleep disturbance in participants at least one month after COVID-19 infection. The prevalence and mean symptom score of each were assessed. RESULTS: Eight hundred and eighty five studies were found, of which 33 were included in the review involving a total of 6743 participants. The studies' risk of bias were typically fair quality. The median study age of participants was 57.8 years (IQR 49.3-60.7), with 63.0% male (IQR 57.0%-73.0%). Participants typically experienced no or mild symptoms of long-term anxiety (GAD-7, STAI-S, HADS) and depression (PHQ-9, BDI, PHQ-2, HADS). Prevalence varied depending on the measurement tool. Sleep disturbances (primarily insomnia) were most commonly reported as mild. PTSD prevalence was similar to anxiety and depression. CONCLUSION: The overall effect of the pandemic has been linked with worsening psychiatric symptoms. However, the long-term effect from direct COVID-19 infection has been associated with no or mild symptoms. Studies exhibited the long-term prevalence of anxiety, depression, PTSD, and sleep disturbances to be comparable to general population levels.

An Ecological Study Assessing the Relationship between Public Health Policies and Severity of the COVID-19 Pandemic.

Reliance on government-led policies have heightened during the COVID-19 pandemic. Further research on the policies associated with outcomes other than mortality rates remains warranted. We aimed to determine associations between government public health policies on the severity of the COVID-19 pandemic. This ecological study including countries reporting ≥25 daily COVID-related deaths until end May 2020, utilised public data on policy indicators described by the Blavatnik school of Government. Associations between policy indicators and severity of the pandemic (mean mortality rate, time to peak, peak deaths per 100,000, cumulative deaths after peak per 100,000 and ratio of mean slope of the descending curve to mean slope of the ascending curve) were measured using Spearman rank-order tests. Analyses were stratified for age, income and region. Among 22 countries, containment policies such as school closures appeared effective in younger populations (rs = -0.620, p = 0.042) and debt/contract relief in older populations (rs = -0.743, p = 0.009) when assessing peak deaths per 100,000. In European countries, containment policies were generally associated with good outcomes. In non-European countries, school closures were associated with mostly good outcomes (rs = -0.757, p = 0.049 for mean mortality rate). In high-income countries, health system policies were generally effective, contrasting to low-income countries. Containment policies may be effective in younger populations or in high-income or European countries. Health system policies have been most effective in high-income countries.

Clinical frailty scale as a point of care prognostic indicator of mortality in COVID-19: a systematic review and meta-analysis.

BACKGROUND: COVID-19 has resulted in the largest pandemic experienced since 1918, accounting for over 2 million deaths globally. Frail and older people are at the highest risk of mortality. The main objective of the present research was to quantify the impact of clinical frailty scale (CFS) by increasing severity of frailty and to identify other personal prognostic factors associated with increased mortality from COVID-19. METHODS: This study offers a contemporary systematic review and meta-analysis to analyse the stratified mortality risk by increasing CFS sub-categories (1-3, 4-5 and 6-9). Databases searched included EMBASE, MEDLINE, CAB Abstracts, PsychInfo, and Web of Science with end-search restriction the 18th December 2020. Publications identified via MedRevix were followed up on the 23rd March 2021 in peer-reviewed database search, and citations were updated as published. Prospective and retrospective cohort studies which reported the association between CFS and COVID-19 mortality were included. Thirty-four studies were eligible for systematic review and seventeen for meta-analysis, with 81-87% (I2) heterogeneity. FINDINGS: All studies [N: 34] included patients from a hospital setting, comprising a total of 18,042 patients with mean age 72.8 (Min: 56; Max: 86). The CFS 4-5 patient group had significantly increased mortality when compared to patients with CFS 1-3 [(RE) OR 1.95 (1.32 (95% CI), 2.87 (95% CI)); I2 81%; p = 0.0008]. Furthermore, CFS 6-9 patient group displayed an even more noticeable mortality increase when compared to patients with CFS 1-3 [(RE) OR 3.09 (2.03, 4.71); I2 87%; p<0.0001]. Generic inverse variance analysis of adjusted hazard ratio among included studies highlighted that CFS (p = 0.0001), male gender (p = 0.0009), National Early Warning Score (p = 0.0001), Ischaemic Heart Disease (IHD) (p = 0.07), Hypertension (HT) (p<0.0001), and Chronic Kidney Disease (CKD) (p = 0.0009) were associated with increased COVID-19 mortality. INTERPRETATION: Our findings suggest a differential stratification of CFS scores in the context of COVID-19 infection, in which CFS 1-3 patients may be considered at lower risk, CFS 4-5 at moderate risk, and CFS 6-9 at high risk of mortality regardless of age. Overall, our study not only aims to alert clinicians of the value of CFS scores, but also highlight the multiple dimensions to consider such as age, gender and co-morbidities, even among moderately frail patients in relation to COVID-19 mortality. FUNDING: None.

The role of C-reactive protein as a prognostic marker in COVID-19.

BACKGROUND: C-reactive protein (CRP) is a non-specific acute phase reactant elevated in infection or inflammation. Higher levels indicate more severe infection and have been used as an indicator of COVID-19 disease severity. However, the evidence for CRP as a prognostic marker is yet to be determined. The aim of this study is to examine the CRP response in patients hospitalized with COVID-19 and to determine the utility of CRP on admission for predicting inpatient mortality. METHODS: Data were collected between 27 February and 10 June 2020, incorporating two cohorts: the COPE (COVID-19 in Older People) study of 1564 adult patients with a diagnosis of COVID-19 admitted to 11 hospital sites (test cohort) and a later validation cohort of 271 patients. Admission CRP was investigated, and finite mixture models were fit to assess the likely underlying distribution. Further, different prognostic thresholds of CRP were analysed in a time-to-mortality Cox regression to determine a cut-off. Bootstrapping was used to compare model performance [Harrell's C statistic and Akaike information criterion (AIC)]. RESULTS: The test and validation cohort distribution of CRP was not affected by age, and mixture models indicated a bimodal distribution. A threshold cut-off of CRP ≥40 mg/L performed well to predict mortality (and performed similarly to treating CRP as a linear variable). CONCLUSIONS: The distributional characteristics of CRP indicated an optimal cut-off of ≥40 mg/L was associated with mortality. This threshold may assist clinicians in using CRP as an early trigger for enhanced observation, treatment decisions and advanced care planning.

Routine use of immunosuppressants is associated with mortality in hospitalised patients with COVID-19.

BACKGROUND: Whilst there is literature on the impact of SARS viruses in the severely immunosuppressed, less is known about the link between routine immunosuppressant use and outcome in COVID-19. Consequently, guidelines on their use vary depending on specific patient populations. METHODS: The study population was drawn from the COPE Study (COVID-19 in Older People), a multicentre observational cohort study, across the UK and Italy. Data were collected between 27 February and 28 April 2020 by trained data-collectors and included all unselected consecutive admissions with COVID-19. Load (name/number of medications) and dosage of immunosuppressant were collected along with other covariate data. Primary outcome was time-to-mortality from the date of admission (or) date of diagnosis, if diagnosis was five or more days after admission. Secondary outcomes were Day-14 mortality and time-to-discharge. Data were analysed with mixed-effects, Cox proportional hazards and logistic regression models using non-users of immunosuppressants as the reference group. RESULTS: In total 1184 patients were eligible for inclusion. The median (IQR) age was 74 (62-83), 676 (57%) were male, and 299 (25.3%) died in hospital (total person follow-up 15,540 days). Most patients exhibited at least one comorbidity, and 113 (~10%) were on immunosuppressants. Any immunosuppressant use was associated with increased mortality: aHR 1.87, 95% CI: 1.30, 2.69 (time to mortality) and aOR 1.71, 95% CI: 1.01-2.88 (14-day mortality). There also appeared to be a dose-response relationship. CONCLUSION: Despite possible indication bias, until further evidence emerges we recommend adhering to public health measures, a low threshold to seek medical advice and close monitoring of symptoms in those who take immunosuppressants routinely regardless of their indication. However, it should be noted that the inability to control for the underlying condition requiring immunosuppressants is a major limitation, and hence caution should be exercised in interpretation of the results. PLAIN LANGUAGE SUMMARY: Regular Use of Immune Suppressing Drugs is Associated with Increased Risk of Death in Hospitalised Patients with COVID-19 Background: We do not have much information on how the COVID-19 virus affects patients who use immunosuppressants, drugs which inhibit or reduce the activity of the immune system. There are various conflicting views on whether immune-suppressing drugs are beneficial or detrimental in patients with the disease. Methods: This study collected data from 10 hospitals in the UK and one in Italy between February and April 2020 in order to identify any association between the regular use of immunosuppressant medicines and survival in patients who were admitted to hospital with COVID-19. Results: 1184 patients were included in the study, and 10% of them were using immunosuppressants. Any immunosuppressant use was associated with increased risk of death, and the risk appeared to increase if the dose of the medicine was higher. Conclusion: We therefore recommend that patients who take immunosuppressant medicines routinely should carefully adhere to social distancing measures, and seek medical attention early during the COVID-19 pandemic.

Following the science? Comparison of methodological and reporting quality of covid-19 and other research from the first wave of the pandemic.

BACKGROUND: Following the initial identification of the 2019 coronavirus disease (covid-19), the subsequent months saw substantial increases in published biomedical research. Concerns have been raised in both scientific and lay press around the quality of some of this research. We assessed clinical research from major clinical journals, comparing methodological and reporting quality of covid-19 papers published in the first wave (here defined as December 2019 to May 2020 inclusive) of the viral pandemic with non-covid papers published at the same time. METHODS: We reviewed research publications (print and online) from The BMJ, Journal of the American Medical Association (JAMA), The Lancet, and New England Journal of Medicine, from first publication of a covid-19 research paper (February 2020) to May 2020 inclusive. Paired reviewers were randomly allocated to extract data on methodological quality (risk of bias) and reporting quality (adherence to reporting guidance) from each paper using validated assessment tools. A random 10% of papers were assessed by a third, independent rater. Overall methodological quality for each paper was rated high, low or unclear. Reporting quality was described as percentage of total items reported. RESULTS: From 168 research papers, 165 were eligible, including 54 (33%) papers with a covid-19 focus. For methodological quality, 18 (33%) covid-19 papers and 83 (73%) non-covid papers were rated as low risk of bias, OR 6.32 (95%CI 2.85 to 14.00). The difference in quality was maintained after adjusting for publication date, results, funding, study design, journal and raters (OR 6.09 (95%CI 2.09 to 17.72)). For reporting quality, adherence to reporting guidelines was poorer for covid-19 papers, mean percentage of total items reported 72% (95%CI:66 to 77) for covid-19 papers and 84% (95%CI:81 to 87) for non-covid. CONCLUSIONS: Across various measures, we have demonstrated that covid-19 research from the first wave of the pandemic was potentially of lower quality than contemporaneous non-covid research. While some differences may be an inevitable consequence of conducting research during a viral pandemic, poor reporting should not be accepted.

The Clinical Frailty Scale: Estimating the Prevalence of Frailty in Older Patients Hospitalised with COVID-19. The COPE Study.

Frailty assessed using Clinical Frailty Scale (CFS) is a good predictor of adverse clinical events including mortality in older people. CFS is also an essential criterion for determining ceilings of care in people with COVID-19. Our aims were to assess the prevalence of frailty in older patients hospitalised with COVID-19, their sex and age distribution, and the completion rate of the CFS tool in evaluating frailty. Methods: Data were collected from thirteen sites. CFS was assessed routinely at the time of admission to hospital and ranged from 1 (very fit) to 9 (terminally ill). The completion rate of the CFS was assessed. The presence of major comorbidities such as diabetes and cardiovascular disease was noted. Results: A total of 1277 older patients with COVID-19, aged ≥ 65 (79.9 ± 8.1) years were included in the study, with 98.5% having fully completed CFS. The total prevalence of frailty (CFS ≥ 5) was 66.9%, being higher in women than men (75.2% vs. 59.4%, p < 0.001). Frailty was found in 161 (44%) patients aged 65-74 years, 352 (69%) in 75-84 years, and 341 (85%) in ≥85 years groups, and increased across the age groups (<0.0001, test for trend). Conclusion: Frailty was prevalent in our cohort of older people admitted to hospital with COVID-19. This indicates that older people who are also frail, who go on to contract COVID-19 may have disease severity significant enough to warrant hospitalization. These data may help inform health care planners and targeted interventions and appropriate management for the frail older person.